The goal of this project is to determine the route and form of clearance of influenza virus (PR/8/34) from the broncho-alveolar spaces to local and systemic lymphoid tissue and to establish the relationship of antigen transport to the development of specific cell-mediated and humoral immunity. We will determine the rate of removal of radioactive antigen from broncho-alveolar spaces and relative uptake by local and systemic lymphoid tissue. Light and electron microscopic studies utilizing peroxidase-labeled antibodies and autoradiography will be used to determine whether degradation of intact viral particles occurs prior to transport across alveolar and/or respiratory epithelium and whether pulmonary macrophages play a role in transport to local lymphoid tissue. Populations of cells derived from local and systemic lymphoid tissue are being analyzed for the presence of specific T cells by proliferative responses to antigen and for B cells by measuring plaque forming cells to determine the correlation between antigen deposition and the development of immune reaction lymphocytes. Finally, the effect of immunity on antigen redistribution and the localization of immune reactive cells will be studied in animals after a second intratracheal instillation in order to determine if antigen is more rapidly cleared or if it results in the emigration of additional antigen reactive cells into the lung.